title: Longin and GAF domains: structural evolution and adaptation to the subcellular trafficking machinery.
abstract: Endomembrane trafficking is one of the most prominent cytological features of eukaryotes. Given their widespread distribution and specialization, coiled-coil domains, coatomer domains, small GTPases and Longin domains are considered primordial 'building blocks' of the membrane trafficking machineries. Longin domains are conserved across eukaryotes and were likely to be present in the Last Eukaryotic Common Ancestor. The Longin fold is based on the α-β-α sandwich architecture and a unique topology, possibly accounting for the special adaptation to the eukaryotic trafficking machinery. The ancient Per ARNT Sim (PAS) and cGMP-specific phosphodiesterases, Adenylyl cyclases and FhlA (GAF) family domains show a similar architecture, and the identification of prokaryotic counterparts of GAF domains involved in trafficking provides an additional connection for the endomembrane system back into the pre-eukaryotic world. Proteome-wide, comparative bioinformatic analyses of the domains reveal three binding regions (A, B and C) mediating either specific or conserved protein-protein interactions. While the A region mediates intra- and inter-molecular interactions, the B region is involved in binding small GTPases, thus providing an evolutionary connection among major building blocks in the endomembrane system. Finally, we propose that the peculiar interaction surface of the C region of the Longin domain allowed it to extensively integrate into the endomembrane trafficking machinery in the earliest stages of building the eukaryotic cell.
authors.affiliation: Molecular Biology and Bioinformatics Unit, Department of Biology, University of Padova, Padova, Italy; Current address: Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Franceschi
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.forename: Alexander
authors.initials: A
authors.lastname: Schlacht
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
authors.forename: Francesco
authors.initials: F
authors.lastname: Filippini
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010944:Plants; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D033921:Vesicular Transport Proteins
keywords: GAF; Last Eukaryotic Common Ancestor; Longin; PAS; architecture; evolution; fold; permutation; protein domain; subcellular trafficking; topology